Insulin-like Growth factor-I Axis Research Articles

Research progress on the correlation between obesity and the occurrence and development of kidney cancer: a narrative review.

Obesity is an important risk factor for the onset of kidney cancer, and the mechanism of obesity leading to the occurrence and development of kidney cancer has been further studied and confirmed in the past decade. The emergence of the "obesity paradox" phenomenon has made the correlation between obesity and the prognosis of kidney cancer survival controversial. This review summarizes the association between obesity and the occurrence and development of kidney cancer based on newly discovered evidence in the past 10 years, in order to provide reference for follow-up research. A comprehensive, non-systematic review of the latest literature was carried out in order to investigate the progress of the correlation between obesity and kidney cancer. PubMed, Web of Science and Embase were being examined and the last run was on July 15, 2024. The correlation between obesity and the occurrence and development of kidney cancer was discussed in this review, and the newly discovered evidence of epidemiology and related mechanisms in the past 10 years was summarized. The latest evidence suggests that obesity is an important risk factor for the development of kidney cancer. Perirenal fat plays an important role in promoting kidney cancer progression and prognosis. Epidemiology shows that the high rates of kidney cancer and obesity coincide in terms of region and ethnicity. The underlying mechanisms associated with obesity in promoting the occurrence and development of kidney cancer mainly include: abnormal expression of adipocytokines, abnormal lipid metabolism, abnormalities in the insulin-like growth factor-I (IGF-I) axis and hyperinsulinemia/insulin resistance, hypoxia and inflammation. As adipose tissue is adjacent to the kidney, the effect of perirenal adipose tissue on the prognosis of kidney cancer is controversial, and some evidence supports the idea of the "obesity paradox".

Growth Hormone and Growth Retardation in Autoimmune Type-1 Diabetes. Insulin an Important Endocrine Growth Factor

Growth hormone (GH) secretory alterations and dysregulations with insulin-like growth factor-I (IGF-1) axis among type-1 diabetic children and adolescents is well established. In this poorly controlled abnormal metabolic state, GH hypersecretion is observed with decreased levels of Insulin-like Growth Factors (IGFs), IGF binding proteins-3 (IGFBP-3), and growth hormone binding protein (GHBP). These all factors results in decreased growth velocity and growth retardation in type-1 diabetic children and adolescents. Insulin is the most important metabolic regulator of this system. Absolute insulin deficiency, as observed in type-1 diabetics, is the primary cause of this dysregulation and alterations. Several published studies have shown that elevated HbA1c and poor glycaemic control are the main factors of this abnormal metabolic state. Conversely, studies have also demonstrated that good glycaemic control with basal bolus insulin regimens or insulin pump can improve diabetic state with restoration of normal growth. Hence this perspective review focuses on these important aspects of growth abnormalities in type-1 diabetic patients and concludes that health care policy makers should develop a close monitoring program and system with multi-disciplinary team approach to prevent further diabetes related growth complications.

The prevalence of IGF-I axis genetic polymorphisms among decathlon athletes

ObjectiveDecathlon is a combined track and field competition, consisting of ten, mainly anaerobic events. Insulin-like growth factor-I (IGF1) axis plays a pivotal role in athletes' structural and functional muscle adaptation to exercise training, and in their competitive performance. Based on the great demand for speed physiological characteristics among decathlon athletes, the aim of this study was to assess the prevalence of IGF genetic polymorphisms among decathletes, to present an optimal genetic profile for enhancing performance. MethodsThe participants included 151 male athletes and 75 male non-athletic controls from Israel and Estonia. Athletes were divided into four groups, according to the field of expertise: (a) 40 sprinters and long jumpers; (b) 40 middle distance runners; (c) 44 Weightlifters; and (d) 27 decathletes. Genomic DNA was extracted from the participants' buccal epithelial cells using standard protocol and then analyzed for IGF1 axis related genetic polymorphism using the allelic discrimination assay. ResultsA significantly higher prevalence of the IGF1 rs35767 TT genotype was found among decathletes compared to the other athletes, as well as a lower prevalence of the IGF1 rs7136446 GG genotype, a higher prevalence of the IGF1R rs1464430 AA genotype, and a higher prevalence of the IGF2 rs680 GG genotype. Moreover, among the decathletes, carriers of the IGF1 rs7136446 GG genotype achieved higher decathlon scores compared to A-allele carriers. ConclusionsThe findings of this study suggest a potential beneficial role for some IGF-axis polymorphisms (mainly the IGF1 1245 TT and the IGF2 GG) among decathletes, both of which are associated with improved speed performance.

Production of recombinant Japanese eel (Anguilla japonica) growth hormones and their effects on early-stage larvae

Growth hormone (Gh) regulates somatic growth in fishes, particularly through the Gh - insulin-like growth factor-I (Igf-I) axis. In this study, recombinant Japanese eel Ghs with or without C-terminal peptides of human chorionic gonadotropin (CTP), which are known to prolong the half-life, were produced using the HEK 293 and CHO expression system. The effect of recombinant Gh administration to eel larvae on their somatic growth was investigated in short-term feeding experiments, and it was found that three types of recombinant Ghs with CTP (CTP-reGh, reGh-CTP and reGh-CTP × 2) were more effective in promoting somatic growth in eel larvae than recombinant Ghs without CTP. Among the three recombinant Ghs with CTP, reGh-CTP × 2 had the highest growth-promoting effects, however only when provided in the short term. After long-term administration of reGh-CTP × 2, there was no difference in growth between the Gh administrated group and the control group. The survival rate of eel larvae were not affected by recombinant Ghs. In addition, the mRNA expression of gh, Gh receptors, Igf-I and IGF-II were measured by quantitative real-time PCR, and significant reductions in the expression of gh, Gh receptors and Igf-I were observed. These findings provide useful tools to study the mechanisms of somatic growth and increase understanding of Gh regulation in anguillid eel larvae.

Morphological changes of the cerebral cortex between children with isolated growth hormone deficiency and idiopathic short stature

The growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis plays an important role in normal brain development, and GH deficiency inevitably affects the growth of the cerebral cortex. This study was designed to analyze morphological differences in gray matter volume, cortical surface area, and gray matter thickness between children with isolated growth hormone deficiency (IGHD) and children with idiopathic short stature (ISS). Twenty-four children with IGHD (mean age 9.42 years, peak GH < 5 μg/l) and 24 controls with ISS (mean age 9.21 years, peak GH > 10 μg/l) were included. High-resolution three-dimensional T1-weighted MRIs were acquired at participants’ first visit. Measurements of gray matter volume, cortical surface area and gray matter thickness were obtained using FreeSurfer. The total and regional differences between groups were statistically analyzed. Correlations between the FreeSurfer results and GH and IGF-I levels were also obtained. The gray matter volume, cortical surface area and gray matter thickness of the total brain and of the bilateral hemispheres of children with IGHD were significantly smaller than those of children with ISS (all P values < 0.05). All the measurements had similar cortical distributions between groups but varied across regions. Cortical regions with significant differences in the mean gray matter volume and surface area were mainly distributed around the bilateral central sulci and the lateral and basal parts of the temporal lobes (all P values < 0.05). There were negative correlations between gray matter volume, cortical surface area and GH levels, and the right hemispheric and total cortical surface area correlated significantly with GH levels (all P values < 0.05) in children with IGHD. There were significant positive correlations between gray matter volume, cortical surface area and IGF-I levels (all P values < 0.05) in both groups, except for in left hemispheric gray matter volume in children with ISS. Children with IGHD have significant morphological changes in the cerebral cortex, which were partially influenced by GH and IGF-I levels. These cortical changes may be related to deficits in their relatively slower development in intelligence, motor performance, and other functions.

Are the Effects of Oral and Vaginal Contraceptives on Bone Formation in Young Women Mediated via the Growth Hormone-IGF-I Axis?

Purpose: Combined hormonal contraceptive therapy has been associated with negative bone mineral density outcomes that may be route-dependent [i.e., combined oral contraception (COC) vs. contraceptive vaginal ring (CVR)] and involve the hepatic growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. The objective of the pilot study was to assess the impact of route of contraceptive administration on IGF-I and procollagen type I N-terminal propeptide (PINP) responses to an IGF-I Generation Test. We hypothesized that the peak rise in IGF-I and PINP concentration and area under the curve (AUC) would be attenuated following COC, but not CVR, use.Methods: Healthy, premenopausal women not taking hormonal contraception were recruited. Women were enrolled in the control group (n = 8) or randomly assigned to COC (n = 8) or CVR (n = 8) for two contraceptive cycles. IGF-I Generation Tests were used as a probe to stimulate IGF-I release and were completed during the pre-intervention and intervention phases. Serum IGF-I and PINP were measured during both IGF-I Generation Tests. The study was registered at ClinicalTrials.gov (NCT02367833).Results: Compared to the pre-intervention phase, peak IGF-I concentration in response to the IGF-I Generation Test in the intervention phase was suppressed in the COC group (p < 0.001), but not the CVR or Control groups (p > 0.090). Additionally, compared to the pre-intervention phase, PINP AUC during the intervention phase was suppressed in both COC and CVR groups (p < 0.001), while no difference was observed in the control group (p = 0.980).Conclusion: These data suggest that changes in recombinant human GH-stimulated hepatic IGF-I synthesis in response to combined hormonal contraception (CHC) use are dependent on route of CHC administration, while the influence on PINP is route-independent. Future research is needed to expand these results with larger randomized control trials in all age ranges of women who utilize hormonal contraception.Clinical Trial Registration: www.ClinicalTrials.gov registration NCT02367833.

SUN-LB61 Differential and Opposite Regulation of Acid Labile Subunit (ALS) Versus Insulin-Like Growth Factor I (IGF-I) by Oral Estrogens in Premenopausal Women

Background: The impact of estrogens (E2) on the growth hormone (GH)/IGF-I axis is known to depend on route of administration: While oral E2 increases GH and decreases IGF-I, transdermal E2 has only limited or no effect. However, data concerning the impact of E2 on IGF binding protein 3 (IGFBP 3) and ALS are less clear. One study in girls demonstrated higher ALS with oral E2, while the opposite was suggested for postmenopausal women. No data are available for healthy premenopausal women.Methods: We measured IGF-I, IGFBP 3 and ALS in fasted healthy adults (93 males (M), 35 premenopausal women without E2-containing oral contraception (FPRE), 37 premenopausal women with E2-containing oral contraception (FPREOC) and 34 postmenopausal women (FPOST)). IGF-I and IGFBP 3 were measured using the IDS-iSYS chemiluminescence immunoassay, and ALS by an in-house immunofluorometric assay (limit of quantification (LoQ) < 50 mU/ml, range 50 - 4000 mU/mL).Results: Median age (range) was 33 (20 - 76), 28 (20 - 44), 24 (21 - 36) and 56 (49 - 70) years for M, FPRE, FPREOC and FPOST, respectively. As expected, IGF-I was lower in FPREOC compared to FPRE (median IGF-I xULN (IQR) 0.56 (0.45 - 0.73) and 0.72 (0.63 – 0.80), P = 0.0017, Kruskal-Wallis). ALS was significantly higher in FPREOC compared to all other groups (mean ALS in M, FPRE, FPREOC and FPOST: 636, 708, 861 and 648 mU/mL, respectively, ANOVA P < 0.0001, Dunnett’s post-hoc test: M vs FPREOC: P < 0.0001, FPRE vs FPREOC: P = 0.0007, FPOST vs FPREOC: P < 0.0001). IGFBP 3 was not different in females with and without oral E2 (median IGFBP 3 xULN (IQR) FPREOC vs FPRE: 0.62 (0.54 - 0.67) vs 0.60 (0.49 – 0.76), Kruskal-Wallis P = 0.295, Dunn’s post-hoc test: P > 0.9999). This was also true between all other groups (Dunn’s post-hoc test: P ≥ 0.4). In our adult cohort, ALS exhibited negative correlation with age (Pearson r = -0.282, P = 0.0003), similar to IGF-I and IGFBP 3. While IGF-I exhibited a moderate negative correlation to BMI (Pearson r = -0.25, P = 0.0013), IGFBP 3 and ALS were not significantly related to BMI.Conclusion: While IGF-I, IGFBP 3 and ALS all are known to be secreted in response to GH, and IGF-I and ALS are assumed to be produced by the same cells in the liver (hepatocytes), the three GH dependent biomarkers appear to be differently regulated by metabolic factors and oral E2. Only IGF-I has some modest association with BMI. Oral E2 is associated with reduced IGF-I, unchanged IGFBP 3 but increased ALS. While the mechanism behind the differential regulation remains to be uncovered, E2 therapy must be taken into account when interpreting IGF-I and ALS concentrations.

Relation of IGF-I with subclinical cardiovascular markers including intima-media thickness, left ventricular mass index and NT-proBNP.

Several studies revealed relations between low or high insulin-like growth factor I (IGF-I) levels and risk of cardiovascular diseases or mortality, whereas the mechanisms behind these associations are still unknown. The study aimed to explore the relations between IGF-I and changes in surrogate markers of cardiovascular disease including carotid intima-media thickness (IMT), left ventricular mass index (LVMI) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Longitudinal data of the population-based cohort Study of Health in Pomerania (SHIP) were used. IMT was measured by ultrasonography and LVMI was determined based on echocardiography. IGF-I and IGF-binding protein-3 (IGFBP-3) levels were measured by chemiluminescent immunoassays and the IGF-I/IGFBP-3 ratio was calculated. Mixed linear regression models adjusted for known cardiovascular confounders were performed. Statistical analyses demonstrated relations between low baseline IGF-I levels (beta for ΔIMT per s.d. increase -0.044 (s.e. 0.012)) or IGF-I/IGFBP-3 ratio (beta -0.045 (0.012)) and a long-term IMT increase. No associations between IGF-I, IGFBP-3 or IGF-I/IGFBP-3 ratio and changes in LVMI were detected. With respect to NT-proBNP sex-specific associations with IGF-I were found. In women, higher baseline IGF-I levels (beta for ΔNT-proBNP per s.d. increase 5.92 (2.2)) or IGF-I/IGFBP-3 ratio (beta 4.48 (2.2)) were related to an increase in NT-proBNP levels. Among men, U-shaped relations of baseline levels of IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio with an increase in NT-proBNP were found. The study detected significant relations between IGF-I and long-term changes in IMT and NT-proBNP but not LVMI. These findings argue for different effects of the IGF-I axis with respect to various cardiovascular entities.

Zinc chloride influences embryonic development, growth, and Gh/Igf-1 gene expression during the early life stage in zebrafish (Danio rerio)

Although zinc is an essential element for organisms, excess zinc exposure is harmful. We assessed the possible negative influence of zinc (Zn) on the freshwater fish Danio rerio during its early life stage by using Organization for Economic Cooperation and Development test guideline no. 210. Lethality of Zn after hatching occurred in a concentration dependent manner. The LC50 and lowest observed effect concentration of mortality values in the present toxicity assay were 2.31 mg/L (95% confidence limit: 1.81–3.05) and 1.5 mg/L, respectively. These values were close to the reported concentration recorded in aquatic environments. Growth inhibition was observed at 15 and 30 days post-hatching with Zn exposure of 1.5 mg/L. In general, the growth hormone (Gh)/insulin-like growth factor-I (Igf-1) axis is important for growth in fishes, and Zn exposure induced a significant reduction of igf-1 expression at the concentration that caused growth inhibition. These findings suggest that the observed growth inhibition was induced by the suppression of igf-1 expression. In addition, these results suggest that by examining gene expression on the Gh/Igf-1 axis, it may be possible to predict growth suppression by chemical exposure.

Role of ghrelin on growth hormone/insulin-like growth factor-1 axis during endotoxemia

ObjectiveTo investigate the anti-inflammatory property of ghrelin treatment on the Growth Hormone (GH)/Insulin-like Growth Factor-I (IGF-1) axis in Wistar rats that have undergone endotoxemia. DesignIn this randomized animal study, lipopolysaccharide (LPS) (5 mg/kg; intraperitoneal) was administered to induce endotoxemia, and ghrelin (15 nmol/kg; endovenous) was injected simultaneously. Blood and liver samples were collected 2 h, 6 h and 12 h after LPS administration for analysis. MeasurementsTumor necrosis factor alpha (TNF-α), interleukin (IL)-1, beta (IL-1β), and IL-6 from both blood and liver were determined by ELISA assay. Serum nitrate was determined by chemiluminescense. Growth hormone receptor (GHR) and growth hormone secretagogue receptor 1a (GHSR-1a) were determined by western blotting. GHR mRNA and IGF-1 mRNA were determined by RT-PCR. ResultsLPS administration induced a decrease in IGF-1 and GH serum levels, characterizing GH/IGF-1 axis disruption. Ghrelin treatment attenuated the decrease of serum levels of IGF-1 as well as the increase of TNF-α, IL-1β, IL-6 and nitrate induced by LPS. The increase of induced GHSR-1a protein expression seen in the LPS group after 2 h remained until 6 h after ghrelin treatment. However, attenuation of the circulating IGF-1 decrease by ghrelin treatment was not accompanied by changes in GHR protein expression nor GHR and IGF-1 gene expression. ConclusionGhrelin was able to attenuate changes in the GH/IGF-1 axis observed during systemic inflammation, which may be due to the modulation of pro-inflammatory mediators release.

Mini Review/Commentary: Growth Hormone Treatment in Children with Type 1 Diabetes.

In the state of insulin deficiency, the growth hormone—insulin-like growth factor-I (GH–IGF-I) axis is altered due to hepatic GH resistance, which leads to GH hypersecretion and low circulating IGF-I concentration. On the other hand, both growth hormone deficiency (GHD) and GH excess have significant influence on carbohydrate metabolism. These complex interactions are challenging in diagnosing GHD in subjects with type 1 diabetes mellitus (T1DM) and in treating subjects with T1DM with GH. So far, there is only limited clinical experience in GH treatment in patients with T1DM, but recently first reports on metabolic safety and efficacy of GH treatment in subjects with T1DM have been published.

Expression of Insulin-like Growth Factor Binding Protein-3 and Regulation of the Insulin-like Growth Factor-I Axis in Pig Testis

The stem cell niche is a complex unit comprising key components, such as the extracellular matrix and various paracrine factors, which regulate the differentiation of adult stem cells. In our previous study, we established pig spermatogonial stem cells (pSSCs) in culture and identified the expression of insulin-like growth factor binding protein-3 (IGFBP-3) in pSSCs. The present study investigated not only the expression of IGFBP-3, but also its possible role in pSSCs. In this study, IGFBP-3-expressing cells responded positively to protein gene product 9.5 (PGP9.5), which is a marker for pig spermatogonia. IGFBP-3 expression was significantly increased in 60-dayold pig testes. Additionally, the expression levels of insulinlike growth factor I (IGF-I) and its receptor (IGF-IR) were observed in pSSCs and pig Sertoli cells (pSCs). Furthermore, IGF-I treatment enhanced the proliferation of pSCs and pSSCs when they were co-cultured. Blocking the IGF-I pathway using a specific IGF-IR inhibitor dramatically reduced the proliferation of pSCs. In addition, when heparan sulfate was used to sequester IGFBP-3 from IGF-I binding, a significant increase in the proliferation of pSCs was observed. Exogenous IGF-I treatment also increased the expression level of IGFBP-3 in cultured pSSCs. Furthermore, pSSCs grew well in IGF-I-treated pSC conditioned media. In summary, IGF-I and IGF-IR signaling are important for the proliferation of pSCs, and the germ cell-derived IGFBP-3 had an inhibitory effect on the mitotic activity of IGF-I in pSCs.

The growth hormone-insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders.

The growth hormone (GH)–insulin-like growth factor (IGF)-I axis is a key endocrine mechanism regulating linear growth in children. While paediatricians have a good knowledge of GH secretion and assessment, understanding and use of measurements of the components of the IGF system are less current in clinical practice. The physiological function of this axis is to increase the anabolic cellular processes of protein synthesis and mitosis, and reduction of apoptosis, with each being regulated in the appropriate target tissue. Measurement of serum IGF-I and IGF-binding protein (IGFBP)-3 concentrations can complement assessment of GH status in the investigation of short stature and contribute to prediction of growth response during GH therapy. IGF-I monitoring during GH therapy also informs the clinician about adherence and provides a safety reference to avoid over-dosing during long-term management.

Growth hormone and insulin-like growth factor-I axis in type 1 diabetes

The precise mechanisms relating type 1 diabetes (T1D) and poor glycemic control to the axis of growth hormone (GH), insulin like growth factor- I (IGF-I), and IGF binding protein-3 (IGFBP-3) remain to be definitively determined. GH resistance with low IGF-I as is frequently seen in patients with T1D is often related to portal hypoinsulization, and lack of upregulation of GH receptors. There are conflicting reports of the effect of a dysregulated GH/IGF-I axis on height in children and adolescents with T1D, as well as on chronic complications. This brief review discusses some of the interactions between the GH/IGF-I axis and T1D pathology, and vice-versa.

The Role of Growth Hormone and Insulin-Like Growth Factor-I in the Liver.

Adult growth hormone deficiency (GHD) is characterized by metabolic abnormalities associated with visceral obesity, impaired quality of life, and increased mortality. Patients with adult GHD show increased prevalence of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), and growth hormone (GH) replacement therapy has been shown to improve these conditions. It has also been demonstrated that a decrease in the GH insulin-like growth factor-I (IGF-I) axis is closely associated with the progression of general NAFLD, suggesting a physiological role of these hormones for the maintenance of the liver. NASH histologically demonstrates inflammation, necrosis, and fibrosis, in addition to steatosis (and is a serious disease because it can progress to liver cirrhosis and hepatocellular carcinoma in a subset of cases). While fibrosis determines the prognosis of the patient, efficacious treatment for fibrosis is crucial; however, it has not yet been established. Recent studies have clarified the essential roles of GH and IGF-I in the liver. GH profoundly reduces visceral fat, which plays an important role in the development of NAFLD. Furthermore, GH directly reduces lipogenesis in the hepatocytes. IGF-I induces cellular senescence and inactivates hepatic stellate cells, therefore ameliorating fibrosis. IGF-I treatment has been shown to improve animal models of NASH and cirrhosis, suggesting potential clinical applications of IGF-I in these conditions. In this review, I will focus on the important roles of GH and IGF-I in the liver, their underlying mechanisms, and their potential therapeutic applications.

Effect of pre- and postpartum supplementation with lipid-encapsulated conjugated linoleic acid on reproductive performance and the growth hormone–insulin-like growth factor-I axis in multiparous high-producing dairy cows

The objective of the study was to evaluate the effect of prepartum and postpartum (PP) supplementation with 2 isomers of conjugated linoleic acid (CLA) on reproductive parameters and some related metabolic factors in dairy cows. High-producing, multiparous Holstein Friesian cows (n = 60) were allotted to 3 treatment groups: the CLA1 group (n = 20) was supplemented with 70 g of lipid-encapsulated CLA providing 7 g each of cis-9,trans-11 and trans-10,cis-12 CLA from d 21 (d 21) before expected calving until d 7 after artificial insemination (AI), that is, until 77 to 91 d PP; the CLA2 group (n = 20) was supplemented with the same amount of CLA beginning at calving until d 7 after AI; and the control group (n = 20) received an isocaloric, isonitrogenous, and isolipidic diet. Blood samples were taken weekly to measure glucose, insulin, insulin-like growth factor-I (IGF-I), and leptin. Liver biopsy was performed in 10 cows per group for growth hormone receptor 1A and IGF-I mRNA analyses. At d 49 to 63 PP, ovulation was synchronized with the Pre-Synch protocol followed by fixed-time AI. Milk progesterone was monitored from calving until d 35 post-AI. Cows returning to estrus following AI were inseminated. Supplementation with CLA before calving improved the recovery of plasma leptin levels in the early PP period (from the day of calving until wk 3 PP; treatment effect). Later PP (wk 5), plasma IGF-I, and leptin remained significantly higher in both CLA1 and CLA2 groups compared with control, although hepatocellular IGF-I mRNA was not different among groups. Plasma IGF-I levels remained higher in both CLA-treated groups on the day of AI. Growth hormone receptor 1A mRNA levels in hepatic tissue decreased in all groups, reaching a nadir in the first week PP. Days to first PP ovulation did not differ between groups; however, both supplemented groups conceived earlier compared with control (d 97 ± 19, d 97 ± 23, and d 113 ± 30 for CLA1, CLA2, and control, respectively). Plasma progesterone concentration was higher in both supplemented groups on d 2 to 5 following the synchronized ovulation than in controls. We concluded that CLA supplementation around calving alters PP metabolic signals as reflected by higher plasma leptin and IGF-I levels. Conjugated linoleic acid stimulated early luteal function and reduced the PP interval to conception.

Dietary vitamin B12 requirement of fingerling blunt snout bream Megalobrama amblycephala determined by growth performance, digestive and absorptive capability and status of the GH-IGF-I axis

This study aimed to investigate the optimal dietary vitamin B12 requirement of fingerling blunt snout bream Megalobrama amblycephala based on the results of growth performance, intestinal digestive and absorptive capability and responses of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis. Fish (initial body weight: 0.71±0.03g) were randomly assigned to six purified diets containing graded levels of vitamin B12 (0, 0.028, 0.051, 0.12, 0.23 and 0.41mg/kg) for 12weeks. Both weight gain (WG) and specific growth rate increased significantly (P<0.05) as dietary vitamin B12 levels increased from 0 to 0.051mg/kg, then plateaued with further increasing levels. Feed conversion ratio decreased as dietary vitamin B12 levels increased from 0 to 0.12mg/kg, but no statistical difference was observed. Whole-body composition and intestinal brush border enzymes activities also exerted little difference within the vitamin B12 range tested, whereas hepatic vitamin B12 contents increased remarkably (P<0.01) with increasing dietary vitamin B12 levels. Intestinal protease, amylase and lipase activities all increased significantly (P<0.05) as dietary vitamin B12 levels increased from 0 to 0.12mg/kg, but decreased remarkably (P<0.05) with further increasing vitamin B12 levels. Similar results were also observed in hepatic IGF-I expressions. Furthermore, the mRNA expressions of GH in the brain decreased significantly (P<0.05) with increasing dietary vitamin B12 levels. Based on the broken-line regression analysis of WG, the optimal dietary vitamin B12 requirement of fingerling blunt snout bream was estimated to be 0.06mg/kg. In addition, a supplementation of 0.12mg/kg vitamin B12 boosted intestinal digestive capability and hepatic IGF-I expression. Statement of relevanceThis study investigated the optimal dietary vitamin B12 requirement of fingerling blunt snout bream based on growth performance. The underlying mechanisms were also investigated with emphasis on intestinal digestive and absorptive capability and modulation of the GH-IGF-I axis. Data obtained here might facilitate the development of low-cost formulated feed for aquatic species.

The Effect of Adenotonsillectomy on Growth in Prepubertal Children

Adenotonsillar hypertrophy (ATH) is the most common cause of obstructive sleep apnea syndrome in children,1 and the prevalence of obstructive sleep apnea syndrome (OSAS) were at least 1–3% in children.2 Sleep disordered breathing (SDB) is often associated with loud snoring, daytime sleepiness, and daytime mouth breathing. Complications of SDB may include failure to thrive, nocturnal enuresis, sweating during sleep, reduced neurocognition, behavioral problem, and school performances.3-5 Several possible mechanisms for failure to thrive have been assessed. Interruption of the insulin-like growth factor-I axis secondary to abnormal nocturnal growth hormone secretion,6 low caloric intake caused by poor appetite and dysphagia,7 recurrent tonsillitis,8 and high energy expenditure as a consequence of increased work of breathing during sleep9 had been proposed as causes. Also many studies had suggested and proved that growth failures were improved after adenotonsillectomy in children with ATH.10-12 On the other hand, obesity could be one of the risk factor for SDB in children.13 There were few studies about the effect of adenotonsillectomy in obesity children, instead it was reported that children who undergo adenotonsillectomy could be at risk to develop overweight in the years after surgery.14 The effect of SDB and adenotonsillectomy on children might be different according to the growth status, but little is known in this aspect. Received: June 8, 2016 Revised: June 17, 2016 Accepted: June 20, 2016

Effect of acute sleep deprivation and recovery on Insulin-like Growth Factor-I responses and inflammatory gene expression in healthy men.

Acute sleep deprivation in humans has been found to increase inflammatory markers and signaling pathways in the periphery through a possible Toll-like receptor 4 (TLR-4). In addition, short duration sleep has been associated with low circulating total Insulin-like Growth Factor-I (IGF-I) concentrations. We aimed to determine whether a total sleep deprivation (TSD) protocol with recovery altered whole-blood gene expression of the proinflammatory cytokines TNF-α and IL-6, as well as TLR-4 expression, and to examine the relationship with circulating concentrations of the IGF-I system. Twelve healthy men participated in a five-day TSD (two control nights followed by one night of sleep deprivation and one night of recovery). Blood was sampled at 0800, before and after sleep deprivation (D2 and D4), and after recovery (D5). It is shown that 25 h of sleep deprivation (D4) induced significant increases in mRNA levels of TNF-α and its soluble receptor R1 (P<0.01 respectively), as well as TLR-4 (P<0.05), while IL-6 mRNA levels remained unchanged. Circulating concentrations of free IGF-I were decreased at D4 (P<0.001). One night of recovery was sufficient to restore basal expression levels for TNF-α, sTNF-R1, TLR-4 and circulating IGF-I. Changes in TLR-4 mRNA levels during the protocol correlated positively with those of TNF-α and sTNF-R1 (r=0.393 and r=0.490 respectively), and negatively with circulating free IGF-I (r=-0.494). In conclusion, 25 h of sleep deprivation in healthy subjects is sufficient to induce transient and reversible genomic expression of the pro-inflammatory cytokine TNF-α and its R1 receptor, and its mediator TLR-4, with a possible link to IGF-I axis inhibition.

Effects of recombinant growth hormone on growth factor and immune component levels in the cinnamon clownfish, Amphiprion melanopus

We investigated the regulatory effects of recombinant growth hormone (rGH) on growth and immunity in an ornamental seawater fish species, the cinnamon clownfish (Amphiprion melanopus). Cinnamon clownfish received intraperitoneal injections of rGH or saline at doses of 0.1 or 1 µg/g, weekly, for 12 weeks. At the end of the experiment, the rGH injection group exhibited the greatest total length (5.3±0.3 and 5.6±0.2 cm, respectively, for the two doses). Moreover, after injection of rGH, the expression levels of pituitary GH mRNA and liver insulin-like growth factor I (IGF-I) mRNA increased significantly (by 18.9-fold and 5.7-fold, respectively), as assessed by quantitative real-time polymerase chain reaction, while the splenic levels of immunoglobulin M protein increased significantly (by 10.5-fold) as assessed by Western blot analysis. Plasma lysozyme and melatonin levels also increased by 2.1- and 1.37-fold, respectively, over those of the control group. Plasma alanine and aspartate aminotransferase levels at 12 weeks (764±46.4 and 3002±101.2 IU/l, respectively) were significantly higher than those at baseline; however, treatment with rGH decreased these values at 12 weeks (276±30.4 and 600.5±59.2 IU/l, respectively). These findings support the hypothesis that rGH plays important roles in the regulation of the GH–IGF-I axis for growth and immunity in the cinnamon clownfish.